The Croonian Lecture, 1971 Cell fusion and the analysis of malignancy

Abstract

The cells of the body do not normally engage in sex. Nor is it easy to see that sexual activity would greatly benefit them. For sex is ultimately merely a device to facilitate the accumulation in a single individual of favourable mutations occurring separately in different individuals; and since the cells in the body are, at least in large part, genetically identical, the advantages to be gained by genetic exchange are obviously limited. In recent years, however, a technique has been devised that imposes a form of artificial sexuality on somatic cells, and it has been found that somatic cells of widely different genetic constitutions can be induced to undergo genetic amalgamation and exchange. A few years ago, Professor Hayes, in a Leeuwenhoek Lecture (Hayes 1966) described how sex in bacteria is mediated by an infectious particle which produces a change in the cell wall of the ‘male’ bacterium that enables it to make intimate contact with the ‘female’ bacterium. A connexion is then established between the cytoplasms of the two bacteria and through this connexion transfer of genetic material may take place. The imposition of sexuality on somatic cells is achieved by a mechanism which, viewed superficially, is reminiscent of bacterial conjugation. An animal virus, whose normal mode of entry into the cell appears to involve fusion between the viral membrane and the cell membrane, is used to facilitate fusion between the cell membranes of contiguous cells (Okada 1958; Harris & Watkins 1965). Cytoplasmic bridges are thus established which eventually determine the complete coalescence of the cytoplasms of adjacent cells (Schneeberger & Harris 1966). In this way multinucleated cells are formed which contain various numbers of nuclei, and different kinds of nuclei if cells of different kinds are brought together (Harris, Watkins, Ford & Schoefl 1966). The virus now commonly used to produce cell fusion is the Sendai virus, a member of the parainfluenza group of myxoviruses, although many other viruses can achieve the same effect. Unlike the sex particle in bacteria, however, Sendai virus will produce fusion of somatic cells even after its nucleic acid has been destroyed (Okada & Tadokoro 1962; Neff & Enders 1968); the viral envelope is all that is required for this effect. The standard reagent for inducing cell fusion is Sendai virus inactivated by large doses of ultraviolet light or by appropriate treatment with β -propriolactone.